Objectives Classification criteria are biased towards classifying long-standing disease. We compared the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR)-2019, Systemic Lupus International Collaborating Clinics (SLICC)-2012 and ACR-1997 criteria in an early (median 48 months) systemic lupus erythematosus (SLE) cohort. Methods Patients diagnosed with SLE (n=690) or control diseases (n=401). Sensitivity, specificity of the criteria and time-to-classification were calculated. Modified classification algorithms were derived from a random 80% and validated in the remaining 20% of the dataset running multiple iterations. Results At last assessment, sensitivities of ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria were 85.7%, 91.3% and 88.6%, with specificities 93.0%, 93.8% and 97.3%, respectively. Both SLICC and EULAR/ACR enabled earlier classification. Only 76.7% of patients with SLE met all three criteria suggesting non-overlapping groups. Notably, unclassified patients had high prevalence of British Isles Lupus Assessment Group moderate/severe manifestations (43.3%–60%) and SLICC/ACR organ damage (30%–50%). At diagnosis, criteria missed 25.6%–30.5% of patients. Modification of EULAR/ACR and SLICC algorithms to include hypocomplementaemia and/or positive anti-phospholipid antibodies as alternative entry criterion, and/or allow classification with fewer clinical criteria from multiple organs, increased their sensitivity at diagnosis (median 82.0% and 86.2%) and overall (93.7% and 97.1%) with modest decreases in specificity. Importantly, patients who were still missed by the modified criteria had lower incidence of major organ involvement, use of immunosuppressive/biological therapies and organ damage. Conclusions The SLICC and EULAR/ACR are more sensitive than the ACR and the EULAR/ACR criteria have superior specificity in early SLE, although patients with significant disease can be missed. Combination and/or modification of the classification algorithms may enhance their sensitivity, allowing earlier classification and treatment of more patients with high disease burden.

Comorbidities and multimorbidity, often complicating the disease course of patients with chronic inflammatory rheumatic diseases, may be influenced by disease-intrinsic and extrinsic determinants including regional and social factors. We analyzed the frequency and co-segregation of self-reported comorbid diseases in a community-based Mediterranean registry of patients (n = 399) with systemic lupus erythematosus (SLE). Predictors for multimorbidity were identified by multivariable logistic regression, strongly-associated pairs of comorbidities by the Cramer’s V-statistic, and comorbidities clusters by hierarchical agglomerative clustering. Among the most prevalent comorbidities were thyroid (45.6%) and metabolic disorders (hypertension: 24.6%, dyslipidemia: 33.3%, obesity: 35.3%), followed by osteoporosis (22.3%), cardiovascular (20.8%), and allergic (20.6%) disorders. Mental comorbidities were also common, particularly depression (26.7%) and generalized anxiety disorder (10.7%). Notably, 51.0% of patients had ≥3 physical and 33.1% had ≥2 mental comorbidities, with a large fraction (n = 86) displaying multimorbidity from both domains. Sociodemographic (education level, marital status) and clinical (disease severity, neurological involvement) were independently associated with physical or mental comorbidity. Patients were grouped into five distinct clusters of variably prevalent comorbid diseases from different organs and domains, which correlated with SLE severity patterns. Conclusively, our results suggest a high multimorbidity burden in patients with SLE at the community, advocating for integrated care to optimize outcomes.

Examining urban–rural differences can provide insights into susceptibility or modifying factors of complex diseases, yet limited data exist on systemic lupus erythematosus (SLE). To study SLE risk, manifestations and severity in relation to urban versus rural residence. Cross-sectional analysis of the Crete Lupus Registry. Demographics, residency history and clinical data were obtained from interviews and medical records (N=399 patients). Patients with exclusively urban, rural or mixed urban/rural residence up to enrolment were compared. The risk of SLE in urban versus rural areas was 2.08 (95% confidence interval: 1.66–2.61). Compared with rural, urban residence was associated with earlier (by almost seven years) disease diagnosis – despite comparable diagnostic delay – and lower female predominance (6.8:1 versus 15:1). Rural patients had fewer years of education and lower employment rates. Smoking was more frequent among urban, whereas pesticide use was increased among rural patients. A pattern of malar rash, photosensitivity, oral ulcers and arthritis was more prevalent in rural patients. Residence was not associated with organ damage although moderate/severe disease occurred more frequently among rural-living patients (multivariable adjusted odds ratio: 2.17, p=0.011). Our data suggest that the living environment may influence the risk, gender bias and phenotype of SLE, not fully accounted for by sociodemographic factors.

To discern predictive factors for incident kidney involvement in patients with SLE. Patients with SLE from the ‘Attikon’ Lupus cohort were monitored for LN, defined by kidney histology and/or classification criteria. Demographic and clinical characteristics at baseline were compared against patients who did not develop LN. LN-free Kaplan–Meier survival curves were generated. A multivariate Cox proportional hazards model was used to identify independent predictors of LN. Independent validation was performed in the University of Crete Lupus registry. Among the 570 patients in the derivation cohort, 59 exhibited LN as their initial presentation, while an additional 66 developed LN during the follow-up period (collectively, 21.9% incidence). In the latter group, baseline factors predictive of subsequent kidney involvement were male sex [multivariable-adjusted hazard ratio (aHR) 4.31; 95% CI: 1.82, 10.2], age of SLE diagnosis below 26 years (aHR 3.71; 95% CI: 1.84, 7.48), high anti-dsDNA titre (aHR 2.48; 95% CI: 1.03, 5.97) and low C3 and/or C4 (although not statistically significant, aHR 2.24; 95% CI: 0.83, 6.05; P = 0.11). A combination of these factors at time of diagnosis conferred an almost 90-fold risk compared with serologically inactive, older, female patients (aHR 88.77; 95% CI: 18.75, 420.41), signifying a very high-risk group. Independent validation in the Crete Lupus registry showed concordant results with the original cohort. Male sex, younger age and serological activity at SLE diagnosis are strongly associated with subsequent kidney involvement. Vigilant surveillance and consideration of early use of disease-modifying drugs is warranted in these subsets of patients.